Exenatide and Impaired Hypoglycaemic Awareness in Type 1 Diabetes

• Status: Completed
• Trial end date: 2018-04-09
• Target enrollment: 0
• Participant gender: All

Summary

Approximately 25% of patients with type 1 diabetes have lost the capacity to timely detect hypoglycaemia, a condition referred to as impaired hypoglycaemic awareness (IHA) that causes a six-fold higher risk of severe, potentially hazardous, hypoglycaemia. IHA is usually the end-result of a process of habituation to recurrent hypoglycemia that is potentially reversible. Treatment with glucagon-like peptide (GLP)-1 Receptor Agonists (1RAs) in addition to insulin therapy may decrease the incidence of hypoglycaemia in patients with type 1 diabetes. This study will test the hypothesis that treatment with the GLP-1RA, exenatide, added to basal-bolus insulin therapy will improve awareness of hypoglycaemia in patients with type 1 diabetes and IHA. In a randomized doubleblind placebo-controlled cross-over trial, patients will be treated for 6 weeks with exenatide (or placebo), after which hypoglycemic symptoms and counterregulatory hormone responses will be examined during a hyperinsulinemic hypoglycemic glucose clamp study.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Radboud University
• Collaborator: AstraZeneca
• Treatments: Exenatide; Hypoglycemic Agents

Criteria

Inclusion Criteria:

• Type 1 diabetes, disease duration >1 year

• Age >18 years, <70 years

• Insulin treatment according to basal-bolus insulin regimen (injections or insulin pump)

• Impaired hypoglycaemic awareness as assessed by a score of 3 or more on the modified Dutch translation of the Clarke questionnaire

• Glycated haemoglobin (HbA1c) ≥42 mmol/mol (6%) and ≤75 mmol/mol (9.0%)

• Ability to provide informed consent

Exclusion Criteria:

• Treatment with incretin-based therapy

• Known intolerance to GLP-1RAs (including allergy)

• Treatment with glucose-modifying or immune-modifying agents, e.g. prednisolon

• Recent history of myocardial infarction or stroke (past year) or laser coagulation for proliferative retinopathy (past 6 months)

• Proliferative retinopathy

• Symptomatic diabetic neuropathy

• Diabetic nephropathy as reflected by albumin-creatinin ratio >30 mmol/mg or estimated Glomerular Filtration Rate (eGFR) <60 ml/min/1.73 m2

• Known heart failure

• History of pancreatitis (acute or chronic) or pancreatic cancer

• Body-mass index >40 kg/m2

• Use of premixed insulin or of long-acting insulin alone

• Total daily insulin dose requirements <20 units unless on pump treatment

• Pregnancy or unwillingness to undertake measures for birth control